Monitoring changes in skin temperature associated with exercise in horses on a water treadmill by use of infrared thermography.

Infrared thermography (IRT) was used to assess surface temperature change as an indirect measure of muscle activity and exercise associated changes in blood flow in the working hind limb muscles of horses (n=7) undergoing water treadmill exercise. Three treatments were investigated including the treadmill ran dry (TD), water at the height of the proximal interphalangeal joint (PIP) and water at the height of the carpus (CP). Maximum skin surface temperature was recorded from the region of the semitendinosus muscle during exercise at each water height. There was a significant difference in surface hind limb temperature between exercise on the water treadmill ran dry and with water at the height of the PIP and CP (P<0.0001) with hotter temperatures recorded during the TD treatment. There was a greater increase in surface temperature of the hind limbs from pre exercise to maximum temperature during the PIP and CP treatments when compared to the TD treatment, however, this was not significant (P=0.58). There was no significant difference in surface hind limb temperature found between exercise in water at the height of the PIP and water at the height of the CP. The findings from this study suggest that IRT is able to non-invasively detect muscle activity and associated changes in blood flow whilst horses are exercised on a water treadmill. IRT could potentially be used as an alternative method to assess muscle activity and temperature change in an aquatic environment where existing methods present methodological challenges.

Development of a sensitive untargeted liquid chromatography-high resolution mass spectrometry screening devoted to hair analysis through a shared MS2 spectra database: A step toward early detection of new psychoactive substances.

Untargeted liquid chromatography-high resolution mass spectrometry (LC-HRMS) techniques have become indispensable tools for systematic toxicological analysis. They allow the research of an almost unlimited number of drugs within a single analytical cycle, but shared mass spectra libraries are still missing to identify newly marketed compounds, along with defined analytical procedures. This article describes the optimization, validation, and application of an untargeted screening method devoted to hair analysis using data-dependent analysis (DDA) and a shared HRMS database. This method used an ultra-high performance liquid chromatography coupled to a benchtop Orbitrap. Raw MS data were processed with Compound Discoverer software coupled to the mzCloud™ library. Optimizations were performed on blank hair spiked with 19 analytes having different physical and chemical properties. To validate the effectiveness of a shared spectra database, 20 compounds spectra were added and then retrospectively screened. Sensitivity and reliability were evaluated on 317 compounds of interest in toxicology. The method was then applied to 11 hair samples. The matrix effect range by ion suppression/enhancement was 40%-110%. The method allows the detection of 284 among the 317 screened compounds, including 72 new psychoactive substances (NPS). Lower limit of identification (LLOI) and lower limit of detection (LLOD) were 1 to 1000 pg/mg and 1 to 500 pg/mg, respectively. The method was successfully applied to 11 clinical cases and 144 compounds were identified including 24 NPS including AKB48-5F for the first time in hair. We developed and validated an LC-HRMS untargeted screening of 284 compounds and successfully applied it to 11 real hair samples.

1,4-Dihydroindeno[1,2-c]pyrazoles as potent checkpoint kinase 1 inhibitors: extended exploration on phenyl ring substitutions and preliminary ADME/PK studies.

A study on substitutions at the four open positions on the phenyl ring of the 1,4-dihydroindeno[1,2-c]pyrazoles as potent CHK-1 inhibitors is described. Bis-substitution at both the 6- and 7-positions led to inhibitors with IC(50) values below 0.3nM. The compound with the best overall activities (36) was able to potentiate the anti-proliferative effect of doxorubicin in HeLa cells by at least 47-fold. Physicochemical, metabolic, and pharmacokinetic properties of selected inhibitors are also disclosed.